It is known that compositions comprising the tunica submucosa of the intestine of warm-blooded vertebrates can be used advantageously as tissue graft materials. See U.S. Pat. Nos. 4,902,508 and 5,281,422. The tissue graft compositions described in those patents are characterized by excellent mechanical properties, including a high burst pressure, and an effective porosity index which allows such compositions to be used beneficially for vascular graft and connective tissue graft constructs. When used in such applications the graft constructs appear not only to serve as a matrix for the regrowth of the tissues replaced by the graft constructs, but, indeed, promote or induce such regrowth of endogenous tissue. Common events to this remodeling process include: widespread and very rapid neovascularization, proliferation of granulation mesenchymal cells, biodegradation/resorption of implanted intestinal submucosal tissue material, and lack of immune rejection.
It is also known that intestinal submucosa can be fluidized by comminuting and/or enzymatic digestion, without loss of its apparent biotropic properties, for use in less invasive methods of administration (e.g., by injection or topical application) to host tissues in need of repair. See U.S. Pat. No. 5,275,826.
There has been much additional research effort directed to finding other natural and synthetic materials having the requisite properties for use as tissue grafts. Surprisingly, it has been found that stomach submucosa prepared by delamination of stomach tissue of warm-blooded vertebrates exhibits mechanical and biotropic properties similar to that which has been reported for intestinal submucosal tissue. It can be substituted for intestinal submucosa tissue in most, if not all, of the applications previously reported for intestinal submucosa.
The tissue graft composition of the present invention comprises stomach submucosa derived from stomach tissue of a warm-blooded vertebrate. The wall of the stomach is composed of the following layers: the tunica mucosa (including an epithelium layer, a tunica propria layer consisting of reticular or fine areolar tissue, and a glandular layer), the tunica submucosa layer (composed of areolar tissue and lacking glands), the tunica muscularis layer (composed of three layers of muscle), and the serosa (a layer of mesothelium outside the loose connective tissue which invests the muscle layers). Blood vessels, lymphatic tissue and neurological tissue also pervade the stomach tissues including the tunica submucosa.
Stomach submucosal tissue in accordance with the present invention compises stomach submucosa delarminated from the glandular portion of the tunica mucosa and the smooth muscle layers of the muscularis externa. The composition has proven to have the ability to induce connective tissue remodeling and wound healing in a fashion very similar to that of intestinal submucosa as described in U.S. Pat. No. 5,275,826. Specifically, the stomach submucosa composition causes cell proliferation in vitro, supports cell growth when used as a growth substrate material, and induces the formation and repair of connective tissue structures such as Achilles tendon when placed in xenogeneic host species. Stomach submucosa appears to be non-antigenic, and induces responses in vivo that are recognized components of wound healing such as neovascularization, cellular infiltration, deposition of extracellular matrix, and eventual degradation and replacement of the implanted material with host tissues. The present graft composition can be implanted or injected into a vertebrate host to induce the repair or replacement of damaged or defective tissues.